Genome-Wide Haplotype Sequence Generation via Optical Mapping
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Solution Overview
Problem
Current optical mapping methods have not been used to generate genome-wide haplotype sequences, despite their effectiveness in creating genome-wide restriction maps for prokaryotic and eukaryotic genomes.
Innovation Solution
The use of optical mapping techniques to produce genome-wide probe maps, which can be analyzed in conjunction with genome-wide restriction maps to generate genome-wide haplotype sequences, employing detectable oligonucleotide probes hybridized to double-stranded nucleic acid molecules and detected using microscopy to create detailed maps of restriction sites and probe locations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If optical mapping methods are used to generate genome-wide restriction maps, then the ability to map restriction sites is improved, but the ability to generate haplotype sequences is insufficient
Solution Approach 1:
The patent extends optical mapping technology to perform multiple functions: generating restriction maps, creating probe maps, and assembling haplotype sequences. By making the optical mapping system universal, it can now address both restriction site mapping and haplotype generation needs through integrated computational methods that combine multiple data sources.
Solution Approach 2:
The patent combines restriction maps and probe maps into a unified haplotype assembly process. By merging these two types of mapping data and integrating them through computational algorithms, the system generates comprehensive haplotype sequences that leverage the strengths of both mapping approaches.
2Loss of information
If multiple mapping approaches are integrated to generate haplotype sequences, then the completeness of genomic information is improved, but the computational complexity increases
Solution Approach 1:
The patent divides the complex haplotype assembly problem into manageable segments by first generating separate restriction maps and probe maps, then processing them through staged computational algorithms. This segmentation allows the system to handle large genomic datasets by breaking them into smaller, computationally tractable units that can be processed and integrated systematically.
Solution Approach 2:
The patent introduces computational algorithms as intermediaries that bridge the gap between raw mapping data and final haplotype sequences. These intermediary processing steps include map assembly, data integration, and sequence reconstruction algorithms that translate multiple mapping approaches into coherent haplotype information without requiring direct complex interactions between all data sources.
3Area of stationary object
If optical mapping is applied to whole genomes instead of clones, then the scope of analysis is improved, but the technical feasibility was previously insufficient
Solution Approach 1:
The patent performs preliminary actions by first generating comprehensive restriction maps and probe maps before attempting haplotype assembly. These preliminary mapping steps prepare the data in advance, organizing it into structured formats that make subsequent whole-genome haplotype reconstruction feasible and reduce the computational burden of handling entire genomes at once.
Solution Approach 2:
The patent replaces traditional mechanical cloning and physical mapping approaches with optical mapping technology that uses light-based detection and computational analysis. This substitution eliminates the need for physical clone manipulation and enables direct whole-genome analysis through optical detection and in silico assembly methods.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach enables the generation of genome-wide haplotype sequences, allowing for the analysis of genomic variations and providing insights into genetic diseases, cancer, and other biological processes, while also being applicable in agricultural and biomedical fields.
Implementation Method 1
employing detectable oligonucleotide probes hybridized to double-stranded nucleic acid molecules
Implementation Method 2
stained with a dye (e.g., a fluorescent dye). The restriction enzyme cleavage sites appear as breakages in the DNA under e.g., a fluorescent microscope
Data Source
AI summary
Methods, computer-accessible medium, and systems for generating a genome wide probe map and/or a genome wide haplotype sequence are provided. In particular, a genome wide probe map can be generated by obtaining a plurality of detectable oligonucleotide probes hybridized to at least one double stranded nucleic acid molecule cleaved with at least one restriction enzyme, and detecting the location of the detectable oligonucleotide probes. For example, genome wide haplotype sequence can be generated by analyzing at least one genome wide restriction map in conjunction with at least one genome wide probe map to determine distances between restriction sites of the at least one genome wide restriction map and locations of detectable oligonucleotide probes of the at least one genome wide probe map and defining a consensus map indicating restriction sites based on each of the at least one genome wide restriction map and locations of detectable oligonucleotide probes based on each of the at least one genome wide probe map.